Lee F Y, Wang S S, Tsai Y T, Lin H J, Lin H C, Chu C J, Wu S L, Tai C C, Lee S D
Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taiwan, Republic of China.
J Hepatol. 1997 Mar;26(3):687-93. doi: 10.1016/s0168-8278(97)80436-9.
BACKGROUND/AIMS: Portal hypertension and hyperdynamic circulation (i.e. generalized vasodilation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy.
Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (approximately 100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation.
In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats (p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index (p<0.05) without changes in portal pressure (p>0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats (p<0.05). Treatment with aminoguanidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats (p>0.05).
The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.
背景/目的：门静脉高压和高动力循环（即全身血管舒张、心输出量增加以及局部器官血流增加）可能在门静脉高压性胃病的发展中起重要作用。本研究调查了对门静脉高压大鼠长期给予选择性诱导型一氧化氮合酶抑制剂氨基胍对血流动力学及门静脉高压性胃病发展的影响。
部分门静脉结扎或假手术大鼠在术前2天及术后14天被随机分为接受安慰剂（蒸馏水）或氨基胍（约100mg/kg皮下注射每日）治疗组。术后14天采用热稀释技术进行血流动力学研究及胃形态学分析。
给予安慰剂的大鼠中，门静脉结扎大鼠的平均动脉压和全身血管阻力显著低于假手术大鼠，而心脏指数和门静脉压力显著高于假手术大鼠（p<0.05）。在门静脉结扎大鼠中，氨基胍使平均动脉压和全身血管阻力显著增加，同时心脏指数显著降低（p<0.05），门静脉压力无变化（p>0.05）。尽管门静脉高压持续存在，但氨基胍治疗的门静脉结扎大鼠的平均动脉压、心脏指数和全身血管阻力与给予安慰剂的假手术大鼠相似。给予安慰剂的门静脉结扎大鼠胃黏膜血管平均横截面积显著高于给予安慰剂的假手术大鼠（p<0.05）。氨基胍治疗在门静脉结扎或假手术大鼠中均未引起胃黏膜血管平均横截面积的变化（p>0.05）。
结果表明，在门静脉高压大鼠中，长期氨基胍治疗可纠正高动力循环，而不引起门静脉压力变化，改善门静脉高压性胃病的发展。本研究提示，门静脉高压性胃病的治疗应旨在降低门静脉压力，而非纠正高动力循环。
